Kifunensine was first isolated from the actinomycete Kitasatosporia kifunense No. 9482 in 1987 (M. Iwami, O. Nakayama. H. Terano, M. Kohsaka, H. Aoki and H. Imanaka, J. Antibiot., 40, 612, 1987) and is a cyclic oxamide derivative of 1-amino-mannojirimycin. Its basic framework combines aspects of oxygenated indolizidine alkaloids with those of the aza sugars.

Kiftnensine is a selective and potent mannosidase inhibitor. It is a very effective inhibitor of the plant glycoprotein processing enzyme mannosidase I (an IC50 of about 2–5×10−8 M was observed against the purified enzyme), but is inactive toward plant mannosidase II (A. D. Elbein, J. E. Tropea, M. Mitchell, and G. P. Kaushal, J. Biol. Chem., 265, 15599, 1990). Kifunensine has also shown promising immunomodulatory activity in α-mannosidase inhibition.
The synthesis of kiflinensine has been reported by both Fujisawa Pharmaceutical Co. (H. Kayakiri, C. Kasahara, T. Oku, and M. Hashimoto, Tetrahedron Lett., 31, 225, 1990, H. Kayakiri, C. Kasahara, K. Nakamura, T. Oku, and M. Hashimoto, Chem. Pharm. Bull., 39, 1392, 1991) and Hudlicky et al. (J. Rouden and T. Hudlicky, J. Chem. Soc. Perkin Trans. 1, 1095, 1993; J. Rouden, T. Hudlicky, H. Luna and S. Allen, J. Am. Chem. Soc., 116, 5099, 1994).
The Fujisawa route produces kifunensine in 8 synthetic steps from mannosamine hydrochloride, which already possesses much of the desired stereochemistry. The process involves the interchange of the C-1 aldehyde and C-6 hydroxymethyl groups of D-mannosamine. The key step is a double cyclisation of an oxamide-aldehyde precursor with ammonia. An overall yield of 33% was reported. It has been found by the applicant that the Fujisawa route does not respond well to scale up and is prone to marked irreproducibility in the silylation step, resulting in a lower overall yield than that reported.
Hudlicky et al. have synthesised kifunesine in a 13 step process starting from achiral chlorobenzene. Chirality is introduced early via a microbial dihydroxylation using Pseudomonas putida 39D. The Hudlicky route involves a microbial oxidation which introduces many complications on scale up. This route also involves the use of hazardous reagents such as sodium azide, mCPBA and ozone.
The applicant has now found that kifunensine may be synthesised from N—acetyl-D-mannosamine, in a manner which avoids, at least in part, some of the abovementioned problems.
It is therefore an object of this invention to provide a novel method of preparing an intermediate[PBl] for the preparation of kifinensine. It is also an object of the invention to provide a method of preparing kifunensine from this intermediate. These objects of the invention are to be read with the alternative object of at least providing the public with a useful choice.